Alcohol-induced DNA damage may be repaired by these two mechanisms

A new study conducted by a group of Dutch researchers at the Nubrecht Institute uncovered two distinct mechanisms capable of repairing deoxyribonucleic acid damage caused by alcohol consumption. The results appeared in the peer-reviewed journal Nature.

According to researchers, consumption of substances like alcohol may induce considerable damage to the DNA. Interstrand crosslinks (ICLs) are associated with a form of DNA damage caused by acetaldehyde, an intermediate in the metabolism of alcohol.

In the study, the exact cause and pathway to repairment of DNA damage caused by acetaldehyde was the primary focus for researchers.

“The nature of the DNA damage induced by acetaldehyde and how this is repaired remains a key question. Here we generate acetaldehyde-induced DNA interstrand crosslinks and determine their repair mechanism in Xenopus egg extracts. We find that two replication-coupled pathways repair these lesions,” researchers stated in the findings.

Based on their findings, researchers examined mechanisms capable of repairing damage from the DNA caused by alcohol consumption. Utilizing protein extracts from the eggs of an African clawed frog, the team were able to turn their attention on two mechanisms and its repair on an interstrand crosslink formed by acetaldehyde.

One of the mechanisms, known as Fanconi anemia pathway, is considered the slower route and “operates using excision—analogous to the mechanism used to repair the interstrand crosslinks caused by the chemotherapeutic agent cisplatin,” the study’s co-authors explained. “However, the repair of acetaldehyde-induced crosslinks results in increased mutation frequency and an altered mutational spectrum compared with the repair of cisplatin-induced crosslinks.”

“The second repair mechanism requires replication fork convergence, but does not involve DNA incisions—instead the acetaldehyde crosslink itself is broken.”

“These results define the repair pathways of DNA interstrand crosslinks caused by an endogenous and alcohol-derived metabolite, and identify an excision-independent mechanism,” the study’s authors concluded.

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